Dental mesenchymal stem cell-derived exosomes for oral diseases: Classification, functionalization and clinical prospects.

The conventional therapeutic approaches for oral diseases primarily encompass dental restoration, pulp therapy, and maxillofacial surgical interventions. However, these methods are difficult to promote tissue regeneration and immune regulation. Mesenchymal stem cell-derived exosomes (MSC-Exos), mainly derived from tissues such as bone marrow, umbilical cord blood, umbilical cord, placenta, and fat, have been used to study the treatment of oral diseases. Conventional MSCs-Exos have relatively low immunogenicity and ethical issues, but exosomes derived from dental mesenchymal stem cells (DSCs) not only have abundant sources but also lower immunogenicity, which can circumvent ethical restrictions. This review aims to comprehensively investigate the isolation and characterization methods of exosomes derived from dental-derived mesenchymal stem cells (DSC-Exos) as well as their sources and biological properties. It further reviews recent advances in their application within the field of stomatology and summarizes various material-based delivery systems for exosomes. Particular emphasis is placed on their therapeutic potential in inflammatory conditions such as pulpitis, periodontitis, temporomandibular joint disorders, and immune-related diseases, as well as the application prospects of inducing cell directional differentiation in pulp-dentin complex regeneration, jawbone repair, and soft tissue regeneration. In addition, we have reviewed here some possible applications of DSC-Exos to prevent orthodontic relapse and treat oral cancer. The DSC-Exos play multiple roles, including anti-inflammatory activity, immunomodulatory effect, and tissue regeneration, and have a great potential in the clinical treatment of oral inflammation, tissue defects, and immune dysregulation. Their therapeutic efficacy could also be improved by combining them with other biomaterials.